A Conversation With NCI Acting Director Doug Lowy

Regardless of the current budgetary constraints and uncertainties set forth by Congress, the National Cancer Institute should be taking advantage of pursing research opportunities in therapeutic responses to immune checkpoint inhibitors and targeting tumor suppressor genes, NCI Acting Director Douglas Lowy, MD, told MedPage Today during a telephone interview.

Lowy was elevated from his previous job as NCI's deputy director following the sudden and surprise resignation in March of his boss, Nobel laureate Harold Varmus, MD, who left to become Lewis Thomas University Professor of Medicine at Weill Cornell Medical College in New York City.

Lowy called in from Vancouver, Canada, where he was honoring a 2-year commitment to attend the World Congress of Dermatology. NCI Media Relations Branch Chief Jenny Haliski was also on the line.

Lowy said that before his appointment April 1 he had not thought about being acting director, but when it happened, "I welcomed the opportunity and have tried to take full advantage of it to make sure the strong forward momentum that we have will continue."

He said he had spent 4 decades running a laboratory at NCI and since the mid-1990s had served as Deputy Director of NCI's intramural program before being tapped by Varmus to become deputy director of the institute in July 2010.

"I've had a fair amount of experience dealing with and understanding the problems, opportunities, and challenges that the Institute has faced," he said, noting that for the first time in his career, his research has had to take a back seat to running the NCI.

He said that during a town hall meeting in early April he told the participants that, if given the choice of going to a lab meeting or testifying before Congress, he'd be testifying.

But he added during the interview that he was not giving up his research, just spending less time on it.

That research has involved basic research on papillomaviruses, as well as the initial development, characterization, and clinical testing of HPV vaccines, leading to the eventual FDA approval of three products.

Lowy has also focused on investigation of cancer genes, including DLC1's role as a tumor suppressor, and is a member of both the National Academy of Sciences and its Institute of Medicine.

But now that focus has shifted to securing NCI's forward motion during a decade of a flat or reduced budget. This year the institute has about $150 million less in buying power than when Lowy became deputy director in 2010.

Obama's proposed 2016 fiscal year budget for NCI includes a 2.9% increase if it is passed, and his Precision Medicine Initiative is one of four research areas that Lowy thinks NCI should be pursuing, along with cancer prevention and screening, cancer health disparities, and basic research.

Permanent Promotion?

It's not clear whether Lowy's "acting" title will become permanent through a presidential appointment. "I serve at the pleasure of the presidential administration and it's up to them if they want to make me regular director or not," he said. "I'm going to try to be as active and vigorous as NCI director whether or not there is 'acting' before the name."

He said he has not and does not have any short-term plans to appoint a deputy director to fill his former position, but that James H. Doroshow, MD, NCI Deputy Director for Clinical and Translational Research and Director of the Division of Cancer Treatment and Diagnosis, has been taking on more activities than he had during Varmus' tenure.

Regarding NCI's prioritizing research areas during a time of great scientific discovery with no certainty of increased funding to support it, Lowy said that it's necessary to continually try to balance medical needs with scientific opportunities, and to try to be invested in areas that are of critical importance to cancer research, giving more or less emphasis depending on what is seen as an opportunity.

He provided two examples in the treatment area that NCI might try to do something.

The first is to take advantage of the evident responses being seen in immune checkpoint inhibitors and to understand more completely how they are working so they can be used more strategically not just as single agents but also in combination.

"If it appears that the checkpoint inhibitors are working especially well where there seem to be a lot of mutations, [then that would] imply that they are working where there is an effective immune response being generated by the inhibitors, which would be important in therapeutic interventions," he said.

The second area involves tumor suppressor genes, which he noted was a "much less mature area," but an important one since so many cancer treatment efforts are aimed toward targeting genes that play a positive role in contributing to the development and maintenance of tumors.

"Since it's inherently more difficult, we've given less emphasis to replacing or reactivating inactivated tumor suppressor genes, and one of the things I'm planning to do later this year is to hold a workshop to see if it's useful for NCI to take a more serious and coordinated role in supporting research with tumor suppressor genes with a translational orientation," he said.

Lowy stressed the importance of striking a balance between making progress in the short term for those who have or will get cancer, while also thinking about research that in the long term will have a great impact on the disease as well.

He said that NCI doesn't want to duplicate the efforts of pharmaceutical companies, but that industry should recognize the potential of certain interventions and support research that it doesn't do but that could materially contribute to understanding mechanisms that can be used in more strategic ways.

Other Initiatives

Lowy also touted the institute's Community Oncology Research Program (NCORP), which complements NCI's cancer centers program and provides access to clinical trials and advances in the standard of care to people in lower-density population areas.

Using Montana as an example -- a state he has come to know on a personal level because his son's family lives there -- he said that through NCORP, information technology, electronic health records, and the recently announced Molecular Analysis for Therapy Choice (NCI-MATCH) program allowing 2,400 sites across the U.S. to access clinical trials, the therapeutic playing field for cancer patients across the country has gotten a lot more level.

He also said that, although it's been really gratifying to see cancer research become more of a "team sport" through multidisciplinary, multi-institutional collaborations, he still believes that some of the important advances made in overall understanding of cancer and interventions will come from investigator-initiated research, and that both models should be supported.

And although some cancer research is being refocused on molecular abnormalities rather than on specific sites of cancer origin, he said that the site-specific Specialized Programs of Research Excellence (SPORE) program will continue but that NCI will also be open to considering SPORE proposals focusing on specific molecular abnormalities as well as specific organ sites.

Lowy said people should not lose sight of the important opportunities to reduce cancer incidence and to diagnose it earlier when it's more amenable to treatment.

"A critical focus of NCI is treating people with cancer but also important over the longer term is preventing cancer and screening in a more efficient and effective manner to interrupt it more effectively."

He said that later this month NCI's two oversight boards, the National Cancer Advisory Board (NCAB) and Board of Scientific Advisors (BSA), will hold a joint meeting, and that he plans to work with them to solidify the oncology part of President Obama's Precision Medicine Initiative, which he hopes will help increase appropriations.

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